An intention-to-treat analysis found no statistically significant difference in the number of laboratory-confirmed all-cause viral respiratory infections among children receiving high doses of vitamin D (2,000 IU/day) compared with those receiving standard doses (IRR 0.97, 95% CI 0.80-1.16), reported Mary Aglipay, of St. Michael's Hospital in Toronto, and colleagues.

No significant difference was observed in time to first infection or parent-reported upper respiratory tract illness, the authors wrote in JAMA.

They noted that viral upper respiratory tract infections are the most common infectious illnesses among kids, and that prior research suggested a potential association between low levels of serum-25-hydroxyvitamin D and increased rates of these illnesses.

But previous studies that attempted to examine the issue were too small, the trial duration was too short, or there was a lack of laboratory-confirmed outcomes. They cited one trial that assessed the effect of vitamin D on upper respiratory infections in children from Japan, but results were mixed.

The Vitamin D Outcomes and Interventions in Toddlers (DO IT) trial was a pragmatic, randomized, superiority trial of healthy children, ages 1 to 5 years, in the TARGet Kids! primary care research network in Toronto. Overall, 703 children were randomized, with 354 receiving the standard dose 400 IU/day of vitamin D (consistent with guidelines from the American Academy of Pediatrics), while 349 received the high dose vitamin D at 2,000 IU/day (within the upper limit of vitamin D intake specified by the Institute of Medicine).

They received these doses in the form of vitamin D drops once per day from September to November until follow up the next year in April and May.

Parents collected nasal swabs from their children through the winter months to be submitted for testing.

Overall, 694 participants had data for the primary analysis. Mean follow-up length and exposure duration was 6 months for both groups. The most prevalent respiratory virus was enterovirus or rhinovirus (n=448 out of 728 swabs testing positive for a virus).

There were 728 laboratory-confirmed upper respiratory infections, although parents reported a total of 1,225 respiratory tract illness episodes. The mean number of laboratory-confirmed upper respiratory infections was one in each group.

The median time to first laboratory-confirmed upper respiratory infection was a little over 3 months in both the high-dose and standard dose groups (3.95 months, 95% CI 3.02-5.95 vs 3.29 months, 95% CI 2.66-4.14, respectively). Both groups had around 600 parent-reported illnesses (625 in standard dose group versus 600 in high-dose group).

When examining specific types of influenza, the authors found a 50% reduction in the rate of influenza A infections. But combined influenza A and B only comprised a small amount of infections in both groups (16 in the high-dose group versus 31 in the standard dose group). The authors also noted that this reduction was "smaller than the minimal clinically important difference."

There was a significant difference in serum 25-hydroxyvitamin D levels among children in the high dose group compared with the standard dose group.

While the authors noted that there was no protective effect observed with high-dose vitamin D among all children, they hypothesized that it might be effective among certain subpopulations. They cited a study that found significantly reduced symptoms linked with daily 4,000 IU vitamin D3 among patients with antibody deficiency, as well as studies suggesting a link between vitamin D and asthma exacerbations.

Study limitations included the fact that at the nasal swabs were parent-collected, so it was possible certain infections were missed without swabs being submitted. In addition, there was no placebo group in this study for ethical reasons (namely that the AAP recommends 400 IU/day of vitamin D). Finally, the study began in late summer, when vitamin D levels were already high for children at baseline.

This study was supported in part by grants from the Canadian government.

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